Positive selection focuses the VH12 B-cell repertoire towards a single B1 specificity with survival function

Immunol Rev. 2004 Feb;197:51-9. doi: 10.1111/j.0105-2896.2004.0098.x.

Abstract

B cells of varying antigen specificities are consistently present in the unmanipulated repertoire. These B cells appear to belong to the marginal zone (MZ) and B1 B-cell subsets and provide protection to the blood and lymph, respectively. Some are specific for self-antigens, suggesting that they are selected based on specificity for self but have a protective role against foreign pathogens. One of these specificities is for phosphatidylcholine (PtC). Anti-PtC B cells comprise 5-8% of the B1 repertoire and are protective against bacterial pathogens. In general, they are restricted to the expression of two VH/Vkappa combinations, VH11/Vkappa9 and VH12/Vkappa4/5H. This review focuses on the differentiation of VH12 anti-PtC B cells. They undergo a series of positive selection events beginning at the pre-B-cell stage that enriches for those with a VHCDR3 and L chain required for PtC binding and eliminating the majority of VH12 B cells that lack the ability to bind PtC. Thus, positive selection focuses the VH12 repertoire toward PtC, ensuring that anti-PtC VH12 B cells are a significant component of the B1-cell repertoire in all individuals.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Animals
  • Antibody Specificity
  • B-Lymphocyte Subsets / cytology
  • B-Lymphocyte Subsets / immunology*
  • Cell Survival
  • Gene Rearrangement, B-Lymphocyte, Heavy Chain*
  • Genes, Immunoglobulin
  • Immunoglobulin Heavy Chains / metabolism
  • Immunoglobulin Light Chains / genetics
  • Immunoglobulin Light Chains / immunology
  • Immunoglobulin Light Chains / metabolism
  • Immunoglobulin Variable Region / genetics
  • Immunoglobulin Variable Region / immunology*
  • Immunoglobulin Variable Region / metabolism
  • Signal Transduction

Substances

  • Immunoglobulin Heavy Chains
  • Immunoglobulin Light Chains
  • Immunoglobulin Variable Region